One aspect of the present invention relates to a therapeutic hydrogel composition where a stabilized form of an antimicrobial complex silver salt is incorporated and further stabilized within a matrix of different polymers and other excipients to form an antimicrobial dressing with properties of pain relief and optimal and accelerated wound healing by creating a dynamic physiological environment suitable for treatment of burns and wounds/lesions.
Bacteria, fungi, and viruses present significant challenges to wound healing, and increase morbidity and mortality. Subsequent wound complications may range from delayed healing, to local and widespread infections, and possible death. Treatment of wounds/lesions such as, but not limited to, second and third degree burns, pressure ulcers, diabetic ulcers, surgical wounds, and various skin abrasions can be difficult to treat in part due to possible infections from microorganisms; and the rise in incidence of superinfections and multiple drug resistant microorganisms.
Infected wounds disrupt the three main phases in wound healing by prolonging the initial inflammatory phase ordinarily lasting one to five days. Once prolonged the second phase known as the proliferative phase generally lasting three to four weeks, and the final phase of epithelialization and tissue remodeling cannot follow the normal wound healing continuum.
Current chemotherapeutic antimicrobial agents have been used topically and systemically for treating and preventing infections in wounds for many years. The current therapy of choice for wound infections is the use of systemic antimicrobials. Systemic use of antimicrobials creates several potential problems including side effects and poor bioavailability to the wound site. This approach is also problematic with the rise in incidence of superinfections with organisms such as Enterobacteriaceae, Pseudomonas, and Candida as well as microbial drug resistance leading to difficult to treat infections such as MRSA (Methicillin Resistant Staphylococcus aureus) and vancomycin-resistant enterococcus (VRE).
The use of topical antimicrobial wound dressings have become significantly more important over the last decade especially in immunocompromised patients such as older adults and patients with diabetes, HIV, burns and those having surgical wounds. These patients are at higher risk for chronic wound infections with prolonged healing times due to the presence of bacteria at greater than 105 to 106 colony forming units/g. This burden of bacteria prolongs the inflammatory phase of wound healing and inhibits the proliferative phase due to increase in protease levels. Consequently, the third phase of wound healing, the epithelialization and tissue remodeling phase, cannot proceed if the initial phases do not advance appropriately.
One of the potential issues faced with chronic wounds is the prolongation of the initial or inflammatory phase due to infection as previously described. Bacteria growth can also lead to changes in metabolic demand with increased levels of protease enzymes. This problem is especially pronounced in diabetic wounds where abnormal metabolic functions are already present. In addition, increased levels of extracellular glucose in diabetic wounds provide an excellent growth media for organisms. As previously mentioned, bioburden microorganism densities greater than 105-106 colony forming units/g are considered a threshold for delayed wound healing and pathology. These wounds have increased exudate, odor, pain and change in color and texture of the wounded tissue. Even in the absence of these signs, infection should be considered if a wound fails to heal in a timely manner. Delay in wound healing may also be due to immune incompetency or poor circulation that is not uncommon in older adults. Wounds such as venous stasis ulcers and decubital ulcers are excellent examples of these types of wounds.
Due to increases in hospital acquired infections with highly multi-drug-resistant bacteria and fungi, surgical wounds are also at risk for infection that can lead to dehiscence or serious delays in healing.
Another health burden seen worldwide, primarily affecting children and young healthy adults are burns. The American Burn Association reported 450,000 patients were treated for burns in hospital emergency departments, hospital outpatient clinics, freestanding urgent care centers or private physician offices. Heat burns and scalds serve as the primary source of injury occurring around the house, with young children at highest risk. Burns are classified as first, second or third degree injuries based on the depth of the injury, with a third degree burn being the most severe resulting in a full thickness wound, i.e. extending into the dermis or subcutaneous tissue. Depending on the severity of the burn, the individual is susceptible to infection. Regardless of the severity the wound is painful. Inflammatory agents are released at the burn site causing swelling and pain at the site of injury. As previously mentioned, secondary bacterial and fungal infections are problematic and delay wound healing or cause more serious consequences, possibly death. The most common organisms that infect burn wounds are Staphylococcus aureus, Group A Streptococcus, Pseudomonas aeruginosa, and Candida. Each of these organisms have the potential to develop multi-drug resistance and the potential to be life threatening.
Cutaneous viral infections can create painful skin lesions that are difficult to heal or take a prolonged time. It is not uncommon for HIV immunosuppressed patients to experience skin lesions from viral infections. The most common virus affecting these patients is Herpes simplex virus (HSV). Varicella zoster/Herpes zoster virus (chicken pox/shingles) is also problematic in HIV patients but may also affect older adults as well as other immunocompromised individuals. Herpes labialis (cold sores) also caused by HSV is also a common cutaneous viral infection that creates painful lesions at the muco-cutaneous junction associated with the lips. These lesions occur in all age groups but especially with individuals under stress and reduced immunocompetence. Many other viruses can impact the skin and cause different types of lesions such as Human papilloma virus (HPV), Poxvirus and Cytomegalovirus (CMV).
Multiple therapeutic approaches have been utilized to deal with healing issues associated with wound infections and burns. It is now widely accepted that moist wound healing is critical for proper healing and acceleration of the process. Combinations of primary dressings, such as hydrogels, or use of different antimicrobial dressings have been employed to help address these issues. The most common topical antibiotics used are mupirocin, clindamycin, erythromycin, gentamicin and the combination of bacitracin, neomycin, and polymyxin B sulfate. These products have limitations related to multi-drug resistance, as well as their formulations having the potential to delay healing. Tolnaftate, nystatin and amphotericin B have commonly been used as topical antifungals. These agents also have the potential to delay healing or demonstrate adverse events. Acyclovir ointment is the most common topical drug for treating HSV; however as an ointment it doesn't provide wound conditions for optimal healing. Additionally, increased resistance to acyclovir is a growing concern. Other topical antiviral products utilized, such as, penciclovir cream and docosanol cream, have shown similar problems in regards to their impact on the wound environment having little or no effect on healing times, other than their antimicrobial effect.
Multiple approaches to treatment are recommended dependent upon the extent and severity of burns. One percent silver sulfadiazine cream is the most commonly used topical antimicrobial treatment for burns. A limitation of this product is its hydrophobic base that presents as a significant problem in removal from the site of injury prior to redressing. Removal can result in significant pain for the patient. Another current treatment of choice, mafenide has a limitation of altering acid-base balance of the wound negatively impacting rate of healing. Newer silver containing products have been introduced; such as a microlattice synthetic hydrogel product that attempts to address some of the associated problems of semisolid emulsion (creams) based products.
The purpose of the present invention is to impact a burn or wound/lesion by decreasing bioburden, pain, healing time, morbidity, and mortality.